Minimal residual disease (MRD) by multiparameter flow cytometry (MFC) is the most effective tool to define a deep response in multiple myeloma (MM). We conducted an MRD correlative study of the EMN02/HO95 MM phase III trial in newly diagnosed MM patients achieving a suspected complete response before maintenance and every 6 months during maintenance. Patients received high-dose melphalan (HDM) versus bortezomib-melphalan-prednisone (VMP) intensification, followed by bortezomib-lenalidomide-dexamethasone (VRd) versus no consolidation, and lenalidomide maintenance. Bone marrow (BM) samples were processed in three European laboratories, applying EuroFlow-based MFC protocols (eight colors, two tubes) with 10-4-10-5 sensitivity. At enrollment in the MRD correlative study, 76% (244/321) of patients were MRD-negative. In the intention-to-treat analysis, after a median follow-up of 75 months, 5-year progression-free survival was 66% in MRD-negative versus 31% in MRD-positive patients (HR 0.39; p < 0.001), 5-year overall survival was 86% versus 69%, respectively (HR 0.41; p < 0.001). MRD negativity was associated with reduced risk of progression or death in all subgroups, including ISS-III (HR 0.37) and high-risk fluorescence in situ hybridization (FISH) patients (HR 0.38;). In the 1-year maintenance MRD population, 42% of MRD-positive patients at pre-maintenance became MRD-negative after lenalidomide exposure. In conclusion, MRD by MFC is a strong prognostic factor. Lenalidomide maintenance further improved MRD-negativity rate.

• MeSH
• Autografts MeSH
• Bortezomib administration & dosage   MeSH
• Bone Marrow Cells metabolism   MeSH
• Dexamethasone administration & dosage   MeSH
• Lenalidomide administration & dosage   MeSH
• Middle Aged MeSH
• Humans MeSH
• Melphalan administration & dosage   MeSH
• Survival Rate MeSH
• Multiple Myeloma * metabolism   mortality   therapy   MeSH
• Disease-Free Survival MeSH
• Antineoplastic Combined Chemotherapy Protocols administration & dosage   MeSH
• Flow Cytometry * MeSH
• Neoplasm, Residual MeSH
• Hematopoietic Stem Cell Transplantation * MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Clinical Trial, Phase III MeSH
• Multicenter Study MeSH
• Research Support, Non-U.S. Gov't MeSH
• Randomized Controlled Trial MeSH
• Names of Substances
• Bortezomib MeSH
• Dexamethasone MeSH
• Lenalidomide MeSH
• Melphalan MeSH